Syntheses of the following six classes of compounds are proposed: a) 2,4-Diamino-5-(1-adamantyl)-6-substitute pyrimidines. b) 2,4- Diamino-5-substituted-6-methylpyrimidines with either -(CH2)n-Adamantyl or CH2-NH-(CH2)2-Adamantyl at carbon 5. c) 2,4-Diamino-6-(or 7) substituted pteridines with either adamantyl or -CO-Adamantyl groups at carbon 6 or 7, respectively. d) 2,4-Diamino- or 2-amino-4- hydroxylpteridines with -CH2NR-Adamantyl side chain at C-6. e) 5- Adamantyl-6-methylpyrimidines having an SH-group at C-2 and C-4 or NH2 group at C-2 and SH group at C-4. f) 2,4-Substituted purines having Adamantyl or -CH2 admantyl groups at N-9. Compounds in classes a-e are designed as inhibitors of dihydrofolate reductase. Class d in addition contains potential blocking agents of biochemical pathways involving tetrahydrofolate cofactors. Compounds in class e are designed as potential inhibitors involved in the interconversion of purines nucleosides or in the biosynthesis of nucleic acids. All compounds synthesized will undergo preliminary screening as growth inhibitors of mammalian cells in culture. Compounds having growth inhibitory activity with ID 5 equals less than 10 minus to the 6th power will be investigated in cell culture for their mode of action and as inibitors of isolated target enzymes. (The most powerful growth inhibitors ID 50 equals less than 10 minus to the 8th power) will undergo testing as antineoplastic agents in vivo in the following systems: L-1210 leukemia, P-788 leukemia, S-180 ascites, S-180 solid tumor. TA3 ascites and spontaneous mammary tumors, all above in mice and Walker carcinoma 256 and Murphy-Sturm Lymphosarcoma in rats. The relationship between antiproliferating activity and the inhibition of target enzymes in vivo will be further examined. C14 and H3 labeled compounds will be prepared for tissue distribution and cellular uptake study. The relationship between hydrophobicity of the C-5 substituent of diaminopyrimidines and their binding to dihydrofolate reductase as well as their cellular uptake will be studied.